Details of the Drug Combination

General Information of Drug Combination (ID: DCKMRGW)

• Drug Combination Name: Levobupivacaine + Phenylephrine
• Indication: Hypotension; Status: Phase 4 [1]
• Component Drugs:
  Levobupivacaine (DM783CH): Small molecular drug
  Phenylephrine (DMZHUO5): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levobupivacaine

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]

Levobupivacaine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[6]

Levobupivacaine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]

Indication(s) of Phenylephrine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[3]
Arrhythmia	BC9Z	Approved	[3]
Common cold	CA00	Approved	[3]
Cough	MD12	Approved	[3]
Fecal incontinence	ME07	Approved	[4]
Fever	MG26	Approved	[3]
Headache	8A80-8A84	Approved	[3]
Mydriasis	LA11.62	Approved	[3]
Ophthalmic graves disease	5A02.0	Approved	[5]
Proctitis	DB33.Z	Approved	[3]
Rhinitis	FA20	Approved	[3]
Seasonal allergic rhinitis	CA08.01	Approved	[3]
Vasomotor/allergic rhinitis	CA08	Approved	[3]

Phenylephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[9]

Phenylephrine Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Expression	[10]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[11]
Carbonic anhydrase 1 (CA1)	OTNFBVVQ	CAH1_HUMAN	Decreases Activity	[12]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[12]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[13]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Secretion	[11]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[13]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[14]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[15]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[15]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[10]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Affects Activity	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[10]
Myosin regulatory light chain 2, atrial isoform (MYL7)	OT7ZNDP4	MLRA_HUMAN	Increases Phosphorylation	[17]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[10]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[10]
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1)	OTC41R1E	RIPK1_HUMAN	Increases Expression	[10]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Affects Activity	[10]
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4)	OTTDCUAO	NFAC4_HUMAN	Increases Localization	[18]
Mixed lineage kinase domain-like protein (MLKL)	OTDSLC81	MLKL_HUMAN	Increases Expression	[10]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[10]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Affects Expression	[19]
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	OTL1D484	RIPK3_HUMAN	Increases Expression	[10]
Pro-adrenomedullin (ADM)	OT7T0TA4	ADML_HUMAN	Decreases Response To Substance	[20]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Response To Substance	[21]
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Affects Response To Substance	[22]
Plasma membrane calcium-transporting ATPase 4 (ATP2B4)	OTMWFDAC	AT2B4_HUMAN	Increases Response To Substance	[23]
Beta-3 adrenergic receptor (ADRB3)	OTPMG4V7	ADRB3_HUMAN	Increases Response To Substance	[24]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Affects Response To Substance	[25]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Response To Substance	[26]
Caveolin-3 (CAV3)	OTWSFDB4	CAV3_HUMAN	Decreases Response To Substance	[27]

References

• [1] ClinicalTrials.gov (NCT02802683) Hemodynamic Impact of Hyperbaric Versus Isobaric for Spinal Anesthesia During Cesarean Delivery
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7211).
• [3] Isoproterenol FDA Label
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019494)
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 485).
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• [17] Key role of myosin light chain (MLC) kinase-mediated MLC2a phosphorylation in the alpha 1-adrenergic positive inotropic effect in human atrium. Cardiovasc Res. 2005 Jan 1;65(1):211-20. doi: 10.1016/j.cardiores.2004.09.019.
• [18] Constrictor-induced translocation of NFAT3 in human and rat pulmonary artery smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L1061-74. doi: 10.1152/ajplung.00096.2005. Epub 2005 Jul 29.
• [19] The haplotype of the growth-differentiation factor 15 gene is associated with left ventricular hypertrophy in human essential hypertension. Clin Sci (Lond). 2009 Oct 19;118(2):137-45. doi: 10.1042/CS20080637.
• [20] Adrenomedullin contributes to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide. Scand J Gastroenterol. 2004 Jul;39(7):686-93. doi: 10.1080/00365520410005306.
• [21] Carvedilol-induced antagonism of angiotensin II: a matter of alpha1-adrenoceptor blockade. J Hypertens. 2006 Jul;24(7):1355-63. doi: 10.1097/01.hjh.0000234116.17778.63.
• [22] Influence of angiotensin-I-converting-enzyme insertion/deletion gene polymorphism on perioperative hemodynamics after coronary bypass graft surgery. J Cardiovasc Surg (Torino). 2008 Apr;49(2):255-60.
• [23] Plasma membrane calcium ATPase overexpression in arterial smooth muscle increases vasomotor responsiveness and blood pressure. Circ Res. 2003 Oct 3;93(7):614-21. doi: 10.1161/01.RES.0000092142.19896.D9. Epub 2003 Aug 21.
• [24] Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management. J Am Coll Cardiol. 2005 Jul 19;46(2):351-9. doi: 10.1016/j.jacc.2005.03.061.
• [25] Tissue-specific expression of human lipoprotein lipase in the vascular system affects vascular reactivity in transgenic mice. Br J Pharmacol. 2002 Jan;135(1):143-54. doi: 10.1038/sj.bjp.0704440.
• [26] Effect of sodium depletion on pressor responsiveness in ACTH-induced hypertension in man. Clin Exp Pharmacol Physiol. 1987 Mar;14(3):237-42. doi: 10.1111/j.1440-1681.1987.tb00382.x.
• [27] Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy. Hypertension. 2003 Aug;42(2):213-9. doi: 10.1161/01.HYP.0000082926.08268.5D. Epub 2003 Jul 7.